Fig. 2 ∣. Segmental heterogeneity of cerebral arteries and diversity of vascular and perivascular cells.

a, The internal carotid artery has a thick layer of SMCs surrounded by nerves arising from cranial autonomic ganglia (extrinsic innervation) embedded in perivascular connective tissue (adventitia). The internal elastic lamina separates SMCs from the endothelial cell monolayer. In the middle cerebral artery (MCA) and pial arteriolar branches, the SMC layer becomes progressively thinner, and a perivascular nerve plexus surrounds the vascular wall. Penetrating arterioles dive into the substance of the brain surrounded by a perivascular space where perivascular macrophages (PVMs) and other cells reside. As the vessel becomes smaller (intraparenchymal arterioles), the vascular basement membrane fuses with the glial basement membrane and perivascular nerves are replaced by nerve terminals from interneurons or subcortical pathways (intrinsic innervation). In capillaries, SMCs are replaced by pericytes. Vascular diameters indicated under the vascular segments refer to the human cerebral circulation. Venous SMCs are morphologically, functionally and molecularly distinct from arterial SMCs. b, Each segment of the cerebrovascular tree is characterized by diverse vascular and perivascular cells. The vascular and astroglial membranes delimit the perivascular space, which disappears when these membranes fuse together. Pial arterioles give rise to penetrating arterioles, the first-order branch of which is defined as precapillary arterioles¹⁴. For mural and endothelial cells, genes enriched in each vascular segment are also indicated. For SMCs, we used the database from ref. ¹³, in which segmental assignment was validated by in situ hybridization. For endothelial cells, we used ref. ¹⁷, in which the segmental assignment was predicted in silico. A–C represents marker endothelial genes at the arteriolar–capillary transition and C–V at the capillary–venular transition. BM, basement membrane; ICA, internal carotid artery.